Noninvasive ultrasound neuromodulation for functional brain mapping

用于功能性大脑绘图的无创超声神经调节

• 批准号: 8392216
• 负责人: Sumon k Pal
• 金额: $ 37.13万
• 依托单位: THYNC, INC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392216
• 关键词: Acoustics; Address; Biological Assay; Brain; Brain Mapping; Brain Part; Brain imaging; Brain region; Characteristics; Computer software; Data; Development; Diagnosis; Diagnostic; Disease; Electrodes; Electroencephalography; Electromagnetics; Electrophysiology (science); Epilepsy; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Human; Image; Individual; Kinetics; Macaca; Medicine; Mental Depression; Methods; Modeling; Nerve; Parkinson Disease; Peripheral Nerve Stimulation; Phase; Physiologic pulse; Primates; Resolution; Scanning; Screening procedure; Series; Signal Transduction; Small Business Innovation Research Grant; Source; Stimulus; System; Techniques; Technology; Testing; Transducers; Translating; Ultrasonic Therapy; Ultrasonography; absorption; cranium; data acquisition; imaging modality; improved; millimeter; nervous system disorder; neuroimaging; neuroregulation; novel; phantom model; programs; research study; response; tool

DESCRIPTION (provided by applicant): Brain mapping tools are essential for both our understanding the brain as well as diagnosing dysfunction. A method to noninvasively and precisely stimulate any three-dimensional locus within the human brain would be transformative, both clinically and scientifically. If compatible with modern functional brain imaging methods, such an improved stimulation tool could support unprecedented studies exploring human brain function and connectivity. Clinically, it could support novel screening/diagnostic strategies and improved treatments for diseases such as depression, Parkinson's, and epilepsy which are becoming more frequently treated using invasive stimulation methods (for example with deep-brain stimulating electrodes; DBS). Pulsed ultrasound (US) energy can be used to modulate brain circuit activity and has the characteristics required to achieve targeted stimulation with millimeter spatial resolution anywhere in the brain. Our goal is to translate ultrasound neuromodulation to humans and develop technologies to combine ultrasound-induced neuromodulation with current neuroimaging and electrophysiology methods. The methods we propose to develop will establish a new paradigm in diagnostic medicine and be broadly applicable to neurological disorders as well as increase our ability to understand integrative functions of the brain. Specific Aim 1. Development of a hardware and software platform for identifying optimal pulsed UNMOD waveforms. Milestone: Hardware and software platform that integrates US stimulation with electrophysiological and fMRI data acquisition to establish a systematic approach for assaying the optimal ultrasound neuromodulation (UNMOD) stimulus parameter space. Specific Aim 2. Development of focusing and scanning strategies for deep neurostimulation through the skull using ultrasound. Milestone: Neuromodulation strategies using multiple sources of ultrasound that offer an improvement in spatial resolution of activation, decrease undesirable thermal effects, and increase in activation efficiency. Specific Aim3. Testing focal neurostimulation strategies in the primate brain. We will use this model to test approaches developed in Specific Aims 1 and 2. Milestone: Proof of concept in primates and the selection of optimal focusing and scanning strategies to be tested in humans. Specific Aim 4. Simultaneous ultrasound nerve stimulation, fMRI imaging and EEG recordings in humans. Milestone: Successful integration of UNMOD, fMRI imaging and EEG recordings in humans. At the successful conclusion of this Phase I SBIR we will have developed a number of key technology pieces for translating functional brain mapping with noninvasive ultrasound neuromodulation in humans. These include the ability to stimulate targeted brain regions through the skull, a proof of concept in primates, and successful integration of UNMOT, fMRI and EEG in humans. We will be poised in Phase II to use this technique to compare the functional brain maps of healthy individuals with ones suffering from neurological disorders. PUBLIC HEALTH RELEVANCE: Brain mapping tools are essential for understanding the brain as well as diagnosing brain dysfunction. We propose to use ultrasound to precisely stimulate parts of the brain, noninvasively, in contrast to current invasive stimulation methods. The methods developed will establish a new paradigm in diagnostic medicine, be broadly applicable to neurological disorders such as depression, Parkinson's, and epilepsy, and increase our ability to understand integrative functions of the brain.

描述（由申请人提供）：大脑映射工具对于我们了解大脑以及诊断功能障碍至关重要。一种非侵袭性和精确刺激人脑内部任何三维基因座的方法在临床和科学上都是变化的。如果与现代功能性脑成像方法兼容，则这种改进的刺激工具可以支持探索人脑功能和连通性的前所未有的研究。在临床上，它可以支持新颖的筛查/诊断策略，并改善抑郁症，帕金森氏症和癫痫病等疾病的治疗方法，这些疾病正在使用侵入性刺激方法（例如，使用深脑刺激电极； DBS）变得越来越频繁地进行治疗。脉冲超声（US）能量可用于调节脑电路活性，并具有实现靶向刺激所需的特征，该刺激在大脑中任何地方的任何地方都具有毫米空间分辨率。我们的目标是将超声神经调节转化为人类，并开发技术，以将超声诱导的神经调节与当前的神经成像和电生理学方法相结合。我们建议开发的方法将在诊断医学方面建立新的范式，并广泛适用于神经系统疾病，并提高我们了解大脑整合功能的能力。特定目的1。开发硬件和软件平台，以识别最佳的脉冲未化学波形。里程碑：硬件和软件平台，将我们与电生理和fMRI数据获取相结合，以建立一种系统的方法来分析最佳的超声神经调节（UMOD）刺激参数空间。特定目的2。使用超声通过头骨进行深层神经刺激的聚焦和扫描策略的发展。里程碑：使用多种超声来源的神经调节策略，可改善激活空间分辨率， 降低不良的热效应，并提高活化效率。特定的AIM3。测试灵长类动物大脑中的局灶性神经刺激策略。我们将使用此模型来测试特定目的1和2的方法。里程碑：灵长类动物的概念证明以及选择在人类中测试的最佳聚焦和扫描策略。特定目的4。在人类中同时进行超声神经刺激，fMRI成像和脑电图记录。里程碑：在人类中成功整合UNMOD，fMRI成像和EEG录音。在此阶段I SBIR的成功结论中，我们将开发许多关键技术，用于将功能性大脑映射转换为人类中非侵入性超声神经调节。其中包括通过头骨刺激有针对性的大脑区域的能力，灵长类动物的概念证明以及人类中的UNMOT，fMRI和EEG的成功整合。我们将在第二阶段中使用该技术来比较健康个体的功能性脑图与患有神经系统疾病的人的功能性脑图。 公共卫生相关性： 大脑映射工具对于理解大脑以及诊断大脑功能障碍至关重要。与当前的侵入性刺激方法相比，我们建议使用超声来精确地刺激大脑的一部分。开发的方法将在诊断医学方面建立新的范式，广泛适用于抑郁症，帕金森氏症和癫痫等神经系统疾病，并提高我们了解大脑整合功能的能力。